Expiratory flow limitation during mechanical ventilation: real-time detection and physiological subtypes.

BACKGROUND: Tidal expiratory flow limitation (EFLT) complicates the delivery of mechanical ventilation but is only diagnosed by performing specific manoeuvres. Instantaneous analysis of expiratory resistance (Rex) can be an alternative way to detect EFLT without changing ventilatory settings. This study aimed to determine the agreement of EFLT detection by Rex analysis and the PEEP reduction manoeuvre using contingency table and agreement coefficient. The patterns of Rex were explored. METHODS: Medical patients ≥ 15-year-old receiving mechanical ventilation underwent a PEEP reduction manoeuvre from 5 cmH2O to zero for EFLT detection. Waveforms were recorded and analyzed off-line. The instantaneous Rex was calculated and was plotted against the volume axis, overlapped by the flow-volume loop for inspection. Lung mechanics, characteristics of the patients, and clinical outcomes were collected. The result of the Rex method was validated using a separate independent dataset. RESULTS: 339 patients initially enrolled and underwent a PEEP reduction. The prevalence of EFLT was 16.5%. EFLT patients had higher adjusted hospital mortality than non-EFLT cases. The Rex method showed 20% prevalence of EFLT and the result was 90.3% in agreement with PEEP reduction manoeuvre. In the validation dataset, the Rex method had resulted in 91.4% agreement. Three patterns of Rex were identified: no EFLT, early EFLT, associated with airway disease, and late EFLT, associated with non-airway diseases, including obesity. In early EFLT, external PEEP was less likely to eliminate EFLT. CONCLUSIONS: The Rex method shows an excellent agreement with the PEEP reduction manoeuvre and allows real-time detection of EFLT. Two subtypes of EFLT are identified by Rex analysis. TRIAL REGISTRATION: Clinical trial registered with www.thaiclinicaltrials.org (TCTR20190318003). The registration date was on 18 March 2019, and the first subject enrollment was performed on 26 March 2019.

The impact of high-fat diet consumption and inulin fiber supplementation on anxiety-related behaviors and liver oxidative status in female Wistar rats.

BACKGROUND: Obesity is a worldwide public health problem associated with cognitive and mental health problems in both humans and rats. Studies assessing the effect of fiber supplementation on behavioral deficits and oxidative stress caused by high-fat diet (HFD) consumption in female rats are still scarce. We hypothesized that HFD consumption would lead to anxiety-related behavior and hepatic oxidative stress and that inulin would protect against these changes. We analyzed the impact of HFD-induced obesity combined with fiber supplementation (inulin) on anxiety-related defensive behavior and hepatic oxidative stress. RESULTS: Female rats were fed a high-fat diet (HFD;45%) for nine weeks to induce obesity. The administration of inulin was found to decrease the adiposity index in both the control and obese groups. The consumption of a HFD combined with inulin supplementation resulted in a reduction in both CAT activity and carbonylated protein levels, leading to a shift in the hepatic redox balance. Interestingly, the behavioral data were conflicting. Specifically, animals that consumed a high-fat diet and received inulin showed signs of impaired learning and memory caused by obesity. The HFD did not impact anxiety-related behaviors in the female rats. However, inulin appears to have an anxiolytic effect, in the ETM, when associated with the HFD. On the other hand, inulin appears to have affected the locomotor activity in the HFD in both open field and light-dark box. CONCLUSION: Our results show that consumption of a HFD induced obesity in female rats, similar to males. However, HFD consumption did not cause a consistent increase in anxiety-related behaviors in female Wistar rats. Treatment with inulin at the dosage used did not exert consistent changes on the behavior of the animals, but attenuated the abdominal WAT expansion and the hepatic redox imbalance elicited by high-fat diet-induced obesity.

Ivabradine restores tonic cardiovascular autonomic control and reduces tachycardia, hypertension and left ventricular inflammation in post-weaning protein malnourished rats.

Malnutrition results in autonomic imbalance and heart hypertrophy. Overexpression of hyperpolarization-activated cyclic nucleotide-gated channels (HCN) in the left ventricles (LV) is linked to hypertrophied hearts and abnormal myocardium automaticity. Given that ivabradine (IVA) has emerging pleiotropic effects, in addition to the widely known bradycardic response, this study evaluated if IVA treatment could repair the autonomic control and cardiac damages in malnourished rats. AIM: Assess the impact of IVA on tonic cardiovascular autonomic control and its relationship with hemodynamics regulation, LV inflammation, and HCN gene expression in post-weaning protein malnutrition condition. MAIN METHODS: After weaning, male rats were divided into control (CG; 22 % protein) and malnourished (MG; 6 % protein) groups. At 35 days, groups were subdivided into CG-PBS, CG-IVA, MG-PBS and MG-IVA (PBS 1 ml/kg or IVA 1 mg/kg) received during 8 days. We performed jugular vein cannulation and electrode implant for drug delivery and ECG registration to assess tonic cardiovascular autonomic control; femoral cannulation for blood pressure (BP) and heart rate (HR) assessment; and LV collection to evaluate ventricular remodeling and HCN gene expression investigation. KEY FINDINGS: Malnutrition induced BP and HR increases, sympathetic system dominance, and LV remodeling without affecting HCN gene expression. IVA reversed the cardiovascular autonomic imbalance; prevented hypertension and tachycardia; and inhibited the LV inflammatory process and fiber thickening caused by malnutrition. SIGNIFICANCE: Our findings suggest that ivabradine protects against malnutrition-mediated cardiovascular damage. Moreover, our results propose these effects were not attributed to HCN expression changes, but rather to IVA pleiotropic effects on autonomic control and inflammation.

Preventive effects of hesperidin in an experimental model ofs acute lung inflammation.

In this study, we hypothesized that long-term administration of hesperidin can modulate the inflammatory response and oxidative stress in animals submitted to mechanical ventilation (MV). Twenty-five C57BL/6 male mice were divided into 5 groups: control, MV, animals receiving hesperidin in three doses 10, 25 and 50 mg/kg. The animals received the doses of hesperidin for 30 days via orogastric gavage, and at the end of the period the animals were submitted to MV. In animals submitted to MV, increased lymphocyte, neutrophil and monocyte/macrophage cell counts were observed in the blood and airways. Associated to this, MV promoted an increase in inflammatory cytokine levels such as CCL2, IL-12 and TNFα. The daily administration of hesperidin in the three doses prevented the effects caused by MV, which was observed by a lower influx of inflammatory cells into the airways, a reduction in inflammatory markers and less oxidative damage.

N-acetylcysteine modulates redox imbalance and inflammation in macrophages and mice exposed to formaldehyde.

This study aimed to evaluate the protective role of N-acetylcysteine (NAC) in cells and mice exposed to formaldehyde. For the in vitro study, J774A.1 macrophages cells were incubated for 8, 16 and 24 h with formaldehyde or NAC to assess cell viability and reactive oxygen species (ROS). In the in vivo study, C57BL/6 mice (n = 48) were divided into 6 groups: control (CG), vehicle (VG) that received saline by orogastric gavage, a group exposed to formaldehyde 1% (FG) and formaldehyde exposed groups that received NAC at doses of 100, 150 and 200 mg/Kg (FN100, FN150 and FN200) for a period of 5 days. In vitro, formaldehyde promoted a decrease in cell viability and increased ROS, while NAC reduced formaldehyde-induced ROS production. Animals exposed to formaldehyde presented higher leukocyte counts in the blood and in the bronchoalveolar lavage fluid, and promoted secretion of inflammatory markers IL-6, IL-15, and IL-10. The exposure to formaldehyde also promoted redox imbalance and oxidative damage characterized by increased activities of superoxide dismutase, catalase, decreased GSH/GSSG ratio, as well as it increased levels of protein carbonyls and lipid peroxidation. NAC administration after formaldehyde exposure attenuated oxidative stress markers, secretion of inflammatory mediators and lung inflammation. In conclusion, both in in vitro and in vivo models, NAC administration exerted protective effects, which modulated the inflammatory response and redox imbalance, thus preventing the development airway injury induced by formaldehyde exposure.

Chronic Oral Administration of Aluminum Hydroxide Stimulates Systemic Inflammation and Redox Imbalance in BALB/c Mice.

The present study is aimed at investigating the long-term effects of the aluminum hydroxide administration in the small intestine, lung, liver, and kidney of male BALB/c mice. The mice received via orogastric gavage phosphate buffered or 10 mg/kg aluminum hydroxide 3 times a week for 6 months. Administration of aluminum hydroxide decreased hemoglobin, hematocrit, and erythrocyte. In the blood, kidney and liver function markers were evaluated, and long-term administration of aluminum hydroxide led to an increase in AST levels and a decrease in urea levels. The animals exposed to aluminum showed higher lipid and protein oxidation in all the organs analyzed. In relation to the enzymes involved in antioxidant defense, the lungs showed lower superoxide dismutase (SOD) and catalase activity and a lower reduced and oxidized glutathione (GSH/GSSG) ratio. In the liver, aluminum administration led to a decrease in catalase activity and the GSH/GSSG ratio. Lower catalase activity was observed in the small intestine, as well as in the lungs and liver. In addition to alterations in antioxidant defense, increased levels of the chemokine CCL-2 were observed in the lungs, lower levels of IL-10 in the liver and small intestine, and decreased levels of IL-6 in the intestine of the animals that received aluminum hydroxide for 6 months. Long-term exposure to aluminum promoted steatosis in the liver. In the kidneys, mice treated with aluminum presented a decreased glomerular density than in the naive control group. In the small intestine, exposure caused villi shortening. Our results indicate that long-term oral administration of aluminum hydroxide provokes systemic histological damage, inflammation, and redox imbalance.

Effects of a lycopene-layered double hydroxide composite administration in cells and lungs of adult mice.

Lycopene is a natural compound with one of the highest antioxidant activities. Its consumption is associated with lower risks in lung cancer and chronic obstructive pulmonary disease, for example. Experimentally, a murine model demonstrated the ingestion of lycopene, which reduced the damage in lungs caused by cigarette smoke. Since lycopene is highly hydrophobic, its formulations in supplements and preparations for laboratory assays are based on oils, additionally, bioavailavility is low. We developed a lycopene layered double hydroxide (Lyc-LDH) composite, which is capable of transporting lycopene aqueous media. Our objective was to evaluate the cytotoxicity of Lyc-LDH and the intra-cellular production of reactive oxygen species (ROS) in J774A.1 cells. Also, in vivo assays were conducted with 50 male C57BL/6 mice intranasally treated with Lyc-LDH 10 mg/kg (LG10), Lyc-LDH 25 mg/kg (LG25) and Lyc-LDH 50 mg/kg (LG50) during five days compared against a vehicle (VG) and control (CG) group. The blood, bronchoalveolar lavage fluid (BALF) and lung tissue were analyzed. The results revealed that Lyc-LDH composite attenuated intracellular ROS production stimulated with lipopolysacharide. In BALF, the highest doses of Lyc-LDH (LG25 and LG50) promoted influx of macrophages, lymphocytes, neutrophils and eosinophils compared to CG and VG. Also, LG50 increased the levels of IL-6 and IL-13, and promoted the redox imbalance in the pulmonary tissue. On the contrary, low concentrations did not produce significative effects. In conclusion, our results suggest that intranasal administration of high concentrations of Lyc-LDH induces inflammation as well as redox status changes in the lungs of healthy mice, however, results with low concentrations open a promising way to study LDH composites as vehicles for intranasal administration of antioxidant coadjuvants.

Long-term e-cigarette aerosol exposure causes pulmonary emphysema in adult female and male mice.

This study aimed to evaluate long-term exposure to conventional cigarette smoke (CC) and electronic cigarette (EC) aerosol in adult male and female C57BL/6 mice. Forty-eight C57BL/6 mice were used, male (n = 24) and female (n = 24), both were divided into three groups: control, CC and EC. The CC and EC groups were exposed to cigarette smoke or electronic cigarette aerosol, respectively, 3 times a day for 60 consecutive days. Afterwards, they were maintained for 60 days without exposure to cigarettes or electronic cigarette aerosol. Both cigarettes promoted an influx of inflammatory cells to the lung in males and females. All animals exposed to CC and EC showed an increase in lipid peroxidation and protein oxidation. There was an increase of IL-6 in males and females exposed to EC. The IL-13 levels were higher in the females exposed to EC and CC. Both sexes exposed to EC and CC presented tissue damage characterized by septal destruction and increased alveolar spaces compared to control. Our results demonstrated that exposure to CC and EC induced pulmonary emphysema in both sexes, and females seem to be more susceptible to EC.

Exogenous surfactant reduces inflammation and redox imbalance in rats under prone or supine mechanical ventilation.

Mechanical ventilation (MV) is a lifesaving therapy for patients with acute or chronic respiratory failure. Despite, it can also cause lung injury by inducing or worsening inflammatory responses and oxidative stress. Several clinical approaches have protective effects on the lungs, including the prone position and exogenous surfactant; however, few studies have evaluated the association between the two strategies, especially in individuals without previous lung injury. We tested the hypothesis that the effects of the homogenization in lung aeration caused by the prone position in association with the anti-inflammatory properties of exogenous surfactant pre-treatment could have a cumulative protective effect against ventilator-induced lung injury. Therefore, Wistar rats were divided into four experimental groups: Mechanical Ventilation in Supine Position (MVSP), Mechanical Ventilation in Prone position (MVPP), Mechanical Ventilation in Supine Position + surfactant (MVSPS), and Mechanical Ventilation in Prone Position + Surfactant (MVPPS). The intranasal instillation of a porcine surfactant (Curosurf®) was performed in the animals of MVSPS and MVPPS 1 h before the MV, all the rats were subjected to MV for 1 h. The prone position in association with surfactant decreased mRNA expression levels of pro-inflammatory cytokines in ventilated animals compared to the supine position; in addition, the NfκB was lower in MVPP, MVSPS and MVPPS when compared to MVSP. However, it had no effects on oxidative stress caused by MV. Pre-treatment with exogenous surfactant was more efficient in promoting lung protection than the prone position, as it also reduced oxidative damage in the lung parenchyma. Nevertheless, the surfactant did not cause additional improvements in most parameters that were also improved by the prone position. Our results indicate that the pre-treatment with exogenous surfactant, regardless of the position adopted in mechanical ventilation, preserves the original lung histoarchitecture, reduces redox imbalance, and reduces acute inflammatory responses caused by mechanical ventilation in healthy adult Wistar rats.

Oxidative Stress and Inflammation in Acute and Chronic Lung Injuries.

Acute and chronic lung injuries are among the leading causes of mortality worldwide. Lung injury can affect several components of the respiratory system, including the airways, parenchyma, and pulmonary vasculature. Although acute and chronic lung injuries represent an enormous economic and clinical burden, currently available therapies primarily focus on alleviating disease symptoms rather than reversing and/or preventing lung pathology. Moreover, some supportive interventions, such as oxygen and mechanical ventilation, can lead to (further) deterioration of lung function and even the development of permanent injuries. Lastly, sepsis, which can originate extrapulmonary or in the respiratory system itself, contributes to many cases of lung-associated deaths. Considering these challenges, we aim to summarize molecular and cellular mechanisms, with a particular focus on airway inflammation and oxidative stress that lead to the characteristic pathophysiology of acute and chronic lung injuries. In addition, we will highlight the limitations of current therapeutic strategies and explore new antioxidant-based drug options that could potentially be effective in managing acute and chronic lung injuries.

Acute Outcomes of Cigarette Smoke and Electronic Cigarette Aerosol Inhalation in a Murine Model.

Cigarette smoking throughout life causes serious health issues in the lungs. The electronic cigarette (E-Cig) use increased, since it was first introduced in the world. This research work compared the short-term exposure consequences to e-cigarette vapor and cigarette smoke in male mice. Forty-five C57BL/6 mice were randomized into control (C) in an ambient air exposition cigarette smoke (CS) and aerosol electronic cigarette (EC), both were exposed to 120 puffs, 3 times/day during five days. Then, in the experimental protocol, the euthanized mice had their tissues removed for analysis. Our study showed that CS and EC resulted in higher cell influx into the airways, and an increase in macrophage counts in CS (209.25 ± 7.41) and EC (220.32 ± 8.15) when compared to C (108.40 ± 4.49) (p < 0.0001). The CS (1.92 ± 0.23) displayed a higher pulmonary lipid peroxidation as opposed to C (0.93 ± 0.06) and EC (1.23 ± 0.17) (p < 0.05). The EC (282.30 ± 25.68) and CS (368.50 ± 38.05) promoted increased levels of interleukin 17 when compared to C (177.20 ± 10.49) (p < 0.05). The EC developed shifts in lung histoarchitecture, characterized by a higher volume density in the alveolar air space (60.21; 55.00-65.83) related to C (51.25; 18.75-68.75) and CS (50.26; 43.75-62.08) (p =0.002). The EC (185.6 ± 9.01) presented a higher respiratory rate related to CS (133.6 ± 10.2) (p < 0.002). Therefore, our findings demonstrated that the short-term exposure to e-cig promoted more acute inflammation comparing to cigarette smoke in the ventilatory parameters of the animals.

The deleterious impact of exposure to different inhaled anesthetics is time dependent.

In this study, the effects of exposure to isoflurane, sevoflurane and desflurane on the oxidative response and inflammation at different times was analyzed in the lungs of adult C57BL/6 mice. 120 animals were divided into 3 groups (n = 40): Isoflurane (ISO), Sevoflurane (SEV) and Desflurane (DES) and exposed to these anesthetics for 1 h (n = 10), 2 h (n = 10) and 3 h (n = 10), at a minimum alveolar concentration (MAC) equal to 1. The control group (CG) (n = 10) was exposed to ambient air. 24 h after the experimental protocol, the animals were euthanized and the bronchoalveolar lavage fluid (BALF), blood and lung tissue samples were collected. In the BALF, animals exposed to isoflurane for 2 h and 3 h showed a greater influx of leukocytes, especially macrophages compared to the CG. The ISO3h had lower leukocyte counts in the peripheral blood compared to CG, ISO1h and ISO2h. There was an increase in CCL-2 levels in the ISO3h compared to the CG. Superoxide dismutase activity was higher in ISO1h compared to CG. The activity of catalase was higher in the ISO1h and ISO2h compared to the CG. The lipid peroxidation, as well as carbonylated protein were higher in the ISO3h compared to the CG (p < 0.05). Similar results were observed in the exposure of SEV and DES compared to inflammation and redox imbalance in different periods. This study demonstrated that time is a determinant to promote a local and systemic inflammatory response to different inhalational anesthetics in a healthy murine model.

Protein restriction during pregnancy affects lung development and promotes oxidative stress and inflammation in C57 BL/6 mice offspring.

OBJECTIVES: The present study aimed to evaluate the effects of maternal protein restriction during pregnancy on the lungs of 1-d and 31-d old offspring of C57BL/6 mice. METHODS: The C57BL/6 mice (8-10 wk) were used for breeding. After pregnancy confirmation, female mice were randomly divided into a control group (CG) receiving a standard diet (22% protein) and a protein-restriction group (PRG) receiving a low-protein diet (6% protein). In the low-protein diet, protein was replaced by carbohydrate. After parturition, female mice that received the low-protein diet were fed the standard diet. Male offspring were euthanized 1 d and 31 d after birth for subsequent analysis. We evaluated the effects of a protein-restricted diet during gestation in pulmonary organogenesis, lung oxidative stress, and pulmonary inflammatory response of the offspring. RESULTS: PRG mice 1 d after birth showed lower body and lung mass, length, relative mass, lung density, and erythrocyte count compared with CG mice. There was an increase in alveolar airspace density and a higher mean linear intercept (Lm), greater oxidative damage, and inflammation in PRG mice compared with CG mice. At 31 d after birth, PRG mice had lower body mass, length, and lung mass values compared with CG mice. PRG mice showed greater recruitment of inflammatory cells to the airways. In addition, there was increased collagen deposition in the lungs, altered inflammatory mediators, and greater oxidative damage compared with CG mice. CONCLUSIONS: Protein restriction during pregnancy reduces the body weight of offspring and promotes inflammation and oxidative stress, resulting in a simplification of the lung structure.

The exogenous surfactant pre-treatment attenuates ventilator-induced lung injury in adult rats.

Mechanical ventilation is an essential supportive therapy in the treatment of critical patients, and it aims to maintain adequate gas exchange; however, it can also contribute to inflammation and oxidative stress, thus leading to lung injury. We tested the hypothesis that exogenous surfactant administration will be protective against ventilator-induced lung injury in adult healthy Wistar rats both because of its anti-inflammatory properties as well as its role in preventing alveolar collapse at end-expiration. Thus, the effect of intranasal instillation of a bovine exogenous surfactant was tested in Wistar rats submitted to mechanical ventilation. The animals were divided into four groups: (1) CONTROL; (2) SURFACTANT; (3) Mechanical ventilation (MV); (4) MV with pre-treatment with surfactant (MVSURFACTANT). The MV and MVSURFACTANT were submitted to MV with high tidal volume (12 mL/kg) for 1 h. After the experimental protocol, all animals were euthanized and the arterial blood, bronchoalveolar lavage fluid and lungs were collected for biochemical, immunoenzymatic assay, arterial blood gases, and morphometric analyzes. The Wistar rats that received exogenous surfactant (Survanta®) by intranasal instillation before MV demonstrated reduced levels of leukocytes, inflammatory biomarkers such as CCL2, IL-1, IL-6 and TNF-α. Furthermore, it prevented oxidative damage by reducing lipid peroxidation and protein carbonylation as well as histological pattern changes of pulmonary parenchyma. Our data indicate that exogenous surfactant attenuated lung inflammation and redox imbalance induced by mechanical ventilation in healthy adult rats suggesting a preventive effect on ventilator-induced lung injury.

Quercetin Improves Pulmonary Function and Prevents Emphysema Caused by Exposure to Cigarette Smoke in Male Mice.

Chronic obstructive pulmonary disease (COPD) is the major cause of morbidity and mortality worldwide, and cigarette smoke is a key factor in the development of COPD. Thus, the development of effective therapies to prevent the advancement of COPD has become increasingly essential. We hypothesized that quercetin protects lungs in mice exposed to long-term cigarette smoke. Thirty-five C57BL/6 mice were exposed to cigarette smoke (12 cigarettes per day) for 60 days and pretreated with 10 mg/kg/day of quercetin via orogastric gavage. After the experimental protocol, the animals were euthanized and samples were collected for histopathological, antioxidant defense, oxidative stress and inflammatory analysis. The animals exposed to cigarette smoke showed an increase in respiratory rate and hematological parameters, cell influx into the airways, oxidative damage and inflammatory mediators, besides presenting with alterations in the pulmonary histoarchitecture. The animals receiving 10 mg/kg/day of quercetin that were exposed to cigarette smoke presented a reduction in cellular influx, less oxidative damage, reduction in cytokine levels, improvement in the histological pattern and improvement in pulmonary emphysema compared to the group that was only exposed to cigarette smoke. These results suggest that quercetin may be an agent in preventing pulmonary emphysema induced by cigarette smoke.

Effects in vitro and in vivo of hesperidin administration in an experimental model of acute lung inflammation.

Mechanical ventilation (MV) is a tool used in critical patient care. However, it can trigger inflammatory and oxidative processes capable of causing or aggravating lung injuries, which is known as ventilator-induced lung injury (VILI). Hesperidin is a flavonoid with antioxidant and anti-inflammatory properties in various diseases. The role of hesperidin in the process triggered by MV is poorly studied. Thus, we hypothesize hesperidin could protect the lung of mice submitted to mechanical ventilation. For that, we evaluated cell viability and reactive oxygen species (ROS) formation in macrophages using different hesperidin concentrations. We observed hesperidin did not reduce cell viability, however; it attenuated the production of intracellular ROS in cells stimulated with lipopolysaccharide (LPS). We further evaluated the effects of hesperidin in vivo in animals submitted to MV. In the bronchoalveolar lavage fluid, there were higher levels of macrophage, lymphocyte and neutrophil counts in animals submitted to MV, indicating an inflammatory process. In the lung tissue, MV induced oxidative damage and increased myeloperoxidase activity, though the antioxidant enzyme activity decreased. MV also induced the production of the inflammatory mediators CCL-2, TNF-α and IL-12. Pretreatment with hesperidin resulted in less recruitment of inflammatory cells to the airways and less oxidative damage. Also, it reduced the formation of CCL-2 and IL-12. Our results show pretreatment with hesperidin can protect the lungs of mice submitted to mechanical ventilation by modulating the inflammatory response and redox imbalance and may act to prevent MV injury.

The effects of different body positions on pulmonary function in healthy adults / Os efeitos de diferentes posições corporais na função pulmonar em adultos saudáveis

Abstract Introduction: Pulmonary function testing, or spirometry, is a validated, globally recognized test that contributes to the diagnosis, staging, and longitudinal follow-up of lung diseases. The exam is most often performed in a sitting position in clinical practice; hence, there are no predicted values for its performance in other positions, such as in different decubitus. Objective: The present study aimed to evaluate the effects of position on pulmonary function test results in healthy adults. Methods: Forty-two healthy adults of both sexes, divided into male (MG) and female groups (FG), were provided respiratory questionnaires. Subsequently, the pulmonary function test was conducted to evaluate the ventilatory parameters of forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and FEV1/FVC ratio in the sitting (S), dorsal decubitus (DD), right lateral decubitus (RLD), and left lateral decubitus (LLD) positions. A comparison of the parametric data was performed via one-way analysis of variance followed by Tukey post-hoc tests. Correlations between the S position variables along with the other positions were evaluated using the Pearson test. Results: The mean and standard error for the FVC values of the MG at positions DD (4.3 ± 0.7/L), RLD (4.1 ± 0.6/L) and LLD (4.1 ± 0.6/L) were lower when compared to S (5.05 ± 0.6 L). There was a strong positive correlation between the values of FVC, FEV1, and FEV1/FVC in the S position compared to other positions analyzed in both groups. Conclusion: Body positioning altered the parameters of the pulmonary function test in healthy adults.

Resumo Introdução: A prova de função pulmonar, ou espirometria, é um teste validado e reconhecido mundialmente que contribui para o diagnóstico, estadiamento e acompanhamento longitudinal das doenças pulmonares. O exame é mais frequentemente realizado na posição sentada na prática clínica; portanto, não há valores previstos para seu desempenho em outras posições, como em decúbitos diferentes. Objetivo: O presente estudo teve como objetivo avaliar os efeitos da posição nos resultados dos testes de função pulmonar em adultos saudáveis. Métodos: Quarenta e dois adultos saudáveis de ambos os sexos, divididos nos grupos masculino (GM) e feminino (GF), receberam questionários respiratórios. Posteriormente, realizou-se o teste de função pulmonar para avaliar os parâmetros ventilatórios de capacidade vital forçada (CVF), volume expiratório forçado no primeiro segundo (VEF1) e relação VEF1/CVF nas posições sentada (S), decúbito dorsal (DD), decúbito lateral direito (DLD) e decúbito lateral esquerdo (DLE). A comparação dos dados paramétricos foi realizada por meio de análise de variância unidirecional seguida do pós-teste de Tukey. As correlações entre as variáveis da posição S com as demais posições foram avaliadas por meio do teste de Pearson. Resultados: A média e o erro padrão dos valores de CVF do MG nas posições DD (4,3 ± 0,7/L), DLD (4,1 ± 0,6/L) e DLE (4,1 ± 0,6/L) foram menores quando comparados com S (5,05 ± 0,6 L). Houve forte correlação positiva entre os valores de CVF, VEF1 e VEF1/CVF na posição S em relação às demais posições analisadas em ambos os grupos. Conclusão: O posicionamento corporal alterou os parâmetros do teste de função pulmonar em adultos saudáveis.

Lycopene Ameliorates Liver Inflammation and Redox Status in Mice Exposed to Long-Term Cigarette Smoke.

Cigarette smoke (CS) is the major cause of preventable death worldwide, and it can also cause damage to extrapulmonary organs, such as the liver, mainly due the generation of reactive oxygen species (ROS). The liver is an essential organ for human survival since it is mainly responsible for the body metabolism and among other things and it is the place where many endogenous and exogenous substances undergo biological transformation. Lycopene is a nonprovitamin A carotenoid found in red fruits and vegetables, and its role as a potent antioxidant is well known. In this study, we hypothesized that lycopene could protect mouse liver against long-term CS exposure. Thirty C57BL/6 mice were exposed to twelve cigarette smoke (12 cigarettes per day) for 60 days and pretreated with 25 mg/kg/day or 50 mg/kg/day of lycopene via orogastric gavage. After euthanasia, the hepatic tissue was collected for histopathological, antioxidant defense, oxidative stress, inflammatory, and collagen deposition analysis. Our analysis demonstrated that lycopene results in a suitable outcome to ameliorate the pathological changes, inflammatory and antioxidant profile in a mouse model of long-term CS exposure, and collagen accumulation in the hepatic extracellular matrix. This study demonstrates for the first time that supplementation of lycopene can be a possible pharmacological tool for the treatment of hepatic damage caused by exposure to long-term CS.

Different Tidal Volumes May Jeopardize Pulmonary Redox and Inflammatory Status in Healthy Rats Undergoing Mechanical Ventilation.

Mechanical ventilation (MV) is essential for the treatment of critical patients since it may provide a desired gas exchange. However, MV itself can trigger ventilator-associated lung injury in patients. We hypothesized that the mechanisms of lung injury through redox imbalance might also be associated with pulmonary inflammatory status, which has not been so far described. We tested it by delivering different tidal volumes to normal lungs undergoing MV. Healthy Wistar rats were divided into spontaneously breathing animals (control group, CG), and rats were submitted to MV (controlled ventilation mode) with tidal volumes of 4 mL/kg (MVG4), 8 mL/kg (MVG8), or 12 mL/kg (MVG12), zero end-expiratory pressure (ZEEP), and normoxia (FiO2 = 21%) for 1 hour. After ventilation and euthanasia, arterial blood, bronchoalveolar lavage fluid (BALF), and lungs were collected for subsequent analysis. MVG12 presented lower PaCO2 and bicarbonate content in the arterial blood than CG, MVG4, and MVG8. Neutrophil influx in BALF and MPO activity in lung tissue homogenate were significantly higher in MVG12 than in CG. The levels of CCL5, TNF-α, IL-1, and IL-6 in lung tissue homogenate were higher in MVG12 than in CG and MVG4. In the lung parenchyma, the lipid peroxidation was more important in MVG12 than in CG, MVG4, and MVG8, while there was more protein oxidation in MVG12 than in CG and MVG4. The stereological analysis confirmed the histological pulmonary changes in MVG12. The association of controlled mode ventilation and high tidal volume, without PEEP and normoxia, impaired pulmonary histoarchitecture and triggered redox imbalance and lung inflammation in healthy adult rats.